Curing HCV Infection Reduces Risk of Liver Cancer by 75%

By Annette M. Boyle

Hashem El-Serag, MD, MPH, chief of Gastroenterology and Hepatology at the Michael E. DeBakey VAMC in Houston, examined veteran Winston Hoyte a few years ago. Photo from MEDVAMC

Hashem El-Serag, MD, MPH, chief of Gastroenterology and Hepatology at the Michael E. DeBakey VAMC in Houston, examined veteran Winston Hoyte a few years ago. Photo from MEDVAMC

HOUSTON — After a decade of dramatically rising rates of hepatocellular carcinoma (HCC) among veterans, aggressive treatment of hepatitis C infections (HCV) appears poised to turn the tide.

In veterans with HCV, achieving a sustained viral response reduces the risk of developing the liver cancer by 75%, according to a new study conducted at the Michael E. DeBakey VAMC in Houston.

In 2002, the VA had 500 patients with a diagnosis of HCC. By 2013, that number had risen nearly tenfold to 4,900, according to David Ross, MD, PhD, director of the VA’s HIV, HCV and public health pathogens programs. Despite improvements in treatment, the cancer has only a 14% five-year survival rate.

About 1.32% of all patients with HCV who are not treated or do not achieve a sustained virologic response will go on to develop HCC each year, said Hashem El-Serag, MD, MPH, chief of gastroenterology and hepatology at the DeBakey VAMC and professor at the Baylor College of Medicine in Houston. In contrast, only 0.32% of those cured of HCV develop hepatocellular carcinoma annually, El-Serag and his colleagues at the VA Center for Innovations in Quality, Effectiveness and Safety found in a study recently published in Hepatology.1

The researchers conducted a retrospective cohort study using data from the VA hepatitis C virus clinical case registry of veterans positive for HCV from October 1999 to August 2009 and followed them through December 2010. Patients were considered to have achieved sustained virologic response (SVR), if they were negative for HCV RNA at least 12 weeks after the conclusion of treatment with interferon with or without ribavirin.

table3Of the 33,005 veterans who received treatment, 10,817 achieved SVR, and 100 developed HCC. Those who had cirrhosis at the time of treatment had nearly seven times the risk of those without cirrhosis, for a 1.39% annual risk.

Diabetes doubled the risk of an HCC diagnosis after SVR. Older age, genotype 3 infection, and Hispanic ethnicity also significantly increased the risk of developing liver cancer.

According to El-Serag, the results are a call to action. “All patients with HCV need to be treated — and soon. The longer we wait, the older they get, and the more cirrhosis and diabetes they get; these will render the HCC preventive effect less optimal,” he told U.S. Medicine.

Early treatment might be even more important with the newer direct-acting antivirals (DAAs). The current treatments result in SVR in more than 90% of patients and are more easily tolerated, but the composition that underlies their easier use and higher cure rates might make them less effective in preventing HCC.

The older, “interferon-based treatments have additional anti-proliferative effects that may augment the cancer prevention effect,” El-Serag noted. Determining whether that translates into lower rates of HCC compared with new therapies will require additional research.

The lower cure rates, grueling regimen and significant side effects meant that patients referred for treatment with the older therapies also lacked other risk factors for HCC. “Most patients cured with interferon-based treatment were likely not active or heavy alcohol drinkers, whereas, with the new medications, this criterion is less important, so those cured today may have higher risk of HCC, but we do not know,” he said.

More than 42,000 veterans have been treated with the newer antiviral agents in the past few years, and more than 60,000 have achieved SVR following treatment with any therapy, according to VA Under Secretary for Health David Shulkin, MD. Because of increased funding and reduced drug pricing, the VA recently announced it will be able to offer the highly effective new therapies to all veterans infected with the disease, regardless of the level of their liver damage.

“The high efficacy and safety of IFN-free DAA in patients with cirrhosis is likely to result in a number of patients with HCV cured and cirrhosis that is much larger than we have observed before,” the study authors noted.

That will make continued surveillance important, said El-Serag. “Those who get cured and have the risk factors (old age, cirrhosis, diabetes) need to be followed up carefully for HCC.”

According to guidelines updated in April by the American Association for the Study of Liver and the Infectious Diseases Society of America (ASSLD), the recommended follow-up for patients without advanced fibrosis is the same as if they were never infected with HCV. The guidelines note that SVR “typically aborts progression of liver injury with regression of liver fibrosis in most, but not all, treated patients.”2

It’s a different story for patients with advanced fibrosis or cirrhosis. They “continue to be at risk for development of hepatocellular carcinoma after achieving an SVR, although the risk in these patients is lower than the risk in persistently viremic patients,” and twice a year ultrasound examinations are recommended by the AASLD.

In addition to regular screening for HCC, El-Serag recommended that physicians work with veterans who have achieved SVR to further reduce their likelihood of developing liver cancer by tackling the risk factors for cirrhosis and diabetes, such as alcohol consumption and obesity.

To better understand the risks veterans face after SVR, El-Serag said, “We need to have an embedded follow-up in the system to monitor the regression/progression of liver disease after cure in order to generate more data to inform the clinical practice.”

1 El-Serag HB, Kanwal F, Richardson P, Kramer J. Risk of Hepatocellular Carcinoma after Sustained Virologic Response in Veterans with HCV-infection. Hepatology. 2016 Mar 4.

2 HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. AASLD and IDSA. April 2016 version.